Novel double brain tumor-targeted lipid material and application thereof

A lipid-targeted and liposome-targeted technology, applied in the field of medicine, can solve problems such as limited targeting ability, inability of drugs to reach more brain tumor tissues, and limited improvement

Active Publication Date: 2018-11-06
SICHUAN UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Glucose or RGD peptide-modified liposomes can improve the brain tumor targeting of drugs to a certain extent and promote the accumulation of drugs in tumor tissues, but this improveme

Method used

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  • Novel double brain tumor-targeted lipid material and application thereof
  • Novel double brain tumor-targeted lipid material and application thereof
  • Novel double brain tumor-targeted lipid material and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Preparation of compound 2

[0038]

[0039] Add succinic anhydride 1 (5.00 g, 49.96 mmol), benzyl alcohol (5.94 g, 54.96 mmol) and 4-dimethylaminopyridine (DMAP, 61 mg, 0.50 mmol) into 50 mL of tetrahydrofuran, heat up to 50 °C The reaction was stirred for 5 hours. Remove the solvent under reduced pressure, add 100 mL of ethyl acetate to the residue, wash with saturated sodium bicarbonate (100 mL), discard the organic layer, adjust the aqueous layer to pH = 2 with dilute hydrochloric acid (1 mol / L), and filter , the filter cake was dried to obtain 6.58 g of white solid, yield 63.29%, Mp:60-62 o c.

Embodiment 2

[0041] Preparation of Compound 4

[0042]

[0043] Anhydrous glucose 3 (Glu, 18.02 g, 0.10 mol) was dissolved in 230 mL of anhydrous pyridine, and after cooling in an ice bath for 5 minutes, trimethylchlorosilane (TMSCl, 76.06 mL, 0.60 mol) and hexamethyl A mixed solution of disilazyl amine (HDMS, 62.88 mL, 0.30 mol) was slowly added dropwise to the above pyridine solution, and stirred at room temperature for 24 hours. Remove the solvent under reduced pressure, add 200 mL of water to disperse, extract the aqueous layer with diethyl ether (200 mL × 2), combine the organic layers, and successively wash with dilute hydrochloric acid (1 mol / L, 200 mL × 2), saturated aqueous sodium chloride (200 mL × 2) Wash, dry over anhydrous sodium sulfate, and remove the solvent under reduced pressure to obtain 52.87 g of yellow oil, with a yield of 97.70%. The product can be directly subjected to the next reaction without purification.

Embodiment 3

[0045] Preparation of Compound 6

[0046]

[0047] Compound 4 (10.99 g, 20.31 mmol) was dissolved in a mixed solution of acetone and methanol (5:8, 65 mL), and acetic acid (2.1 mL, 36.72 mmol) in acetone and methanol (5:8) was slowly added dropwise under ice cooling. 8, 6.5 mL) mixed solution. After the dropwise addition, the reaction solution was moved to room temperature and stirred for 2 hours, and sodium carbonate powder (3.30 g, 31.14 mmol) was added to continue stirring at room temperature for 20 minutes. The white solid was removed by filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (petroleum ether / ethyl acetate=50 / 1) to obtain 7.40 g of a colorless oil with a yield of 77.65%. 1 H NMR (400 MHz, CDCl 3 , ppm) δ : 0.12-0.18 (m, 36 H), 3.31-0.34 (m, 1 H), 3.37 (dd, 1 H, J = 2.8 Hz, 9.2 Hz), 3.55(t, 1 H, J = 8.8 Hz), 3.62-3.64 (m, 3H), 3.79 (t, 1 H, J = 8.8 Hz), 5.02 (d,1 H, J =...

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Abstract

The invention discloses a novel lipid material. The novel lipid material is used for prolonging the circulating time and increasing the transfer amount of medicine to brain tumor tissues in a target way. The novel lipid material is characterized in that polyethylene glycol is used as a bridge, one side of the bridge is connected with cholesterol, and one side of the bridge is connected with glucose and RGD (arginine-glycine-aspartic acid) peptide, so that the lack of brain tumor targeting ability by the lipid modified by the single glucose or the RGD peptide is overcome, and the brain tumor can be effectively targeted after blood brain barrier crossing. The novel lipid material can be used for different preparation types of lipids, nanoparticles, micelles and the like; the prepared paclitaxel-carrying lipid has obvious brain tumor targeting function, and broad application prospect.

Description

technical field [0001] The present invention relates to a new type of lipid material and its application in the drug delivery system, which has the functions of prolonging the internal circulation and double brain tumor targeted drug delivery, including the preparation of the material and its function as a drug carrier in drug delivery The application belongs to the technical field of medicine. Background technique [0002] According to statistics, about 1 / 5 of the world's population suffers from various types and degrees of central nervous system (CNS) diseases, including brain tumors, acute or chronic pain syndrome, epilepsy, encephalitis, cerebral ischemia and neurodegeneration Diseases (e.g. Alzheimer's, Parkinson's, etc.). As the world's population ages, this trend will intensify and have serious implications for human health. The existence of the blood-brain barrier (BBB) ​​has a certain protective effect on the human central nervous system, but it also restricts man...

Claims

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Application Information

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IPC IPC(8): A61K47/24A61K47/54A61K47/64A61K31/337A61K47/69A61P35/00
CPCA61K47/24A61K47/549A61K47/64A61K47/6911A61P35/00A61K31/337
Inventor 吴勇海俐郭丽赵毅乐其明陈洋付秋旖
Owner SICHUAN UNIV
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